The team demonstrated how purines and pyrimidine nucleotides can both be assembled on the same sugar scaffold to form molecules called ribonucleotides which are used to construct RNA.

Purine and pyrimidine nucleotides are used to create the DNA and RNA. The purine and pyrimidine nucleotides bind to one another through specific molecular interactions that provide a mechanism to copy and transfer information at the molecular level, which is essential for genetics, replication and evolution. Therefore understanding the origins of nucleotides is thought to be key to understanding the origins of life itself.

The team discovered that molecules, called 8-oxo-adenosine and 8-oxo-inosine, which are purine ribonucleotides, can be formed under the same chemical conditions as the natural pyrimidine ribonucleotides. They also found that one chemical precursor can divergently yield both purine and pyrimidine ribonucleotides.

"The mechanism we've reported gives both classes of molecule the same stereochemistry that is universally found in the sugar scaffold of biological nucleic acids, suggesting that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids," said Dr Shaun Stairs (UCL Chemistry), first author of the study.

Date: May 17, 2017
Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences
Summary:

Debate exists over how life began on Earth, but a new study provides evidence for a 'metabolism-first' model. Scientists have traced the origins and evolution of molecular functions through time. The study shows metabolism and binding arose first, followed by the functional activities of larger macromolecules and cellular machinery.

The hypothesis:

Caetano-Anollés and Ibrahim Koç, a visiting scholar in the department, found evidence for the "metabolism-first" hypothesis by studying the evolution of molecular functions in organisms representing all realms of life. For 249 organisms, their genomes -- or complete set of genes -- were available in a searchable database. What's unique about this particular resource, known as the Gene Ontology (GO) database, is the fact that for each gene product -- a protein or RNA molecule -- a set of terms describing its function goes with it.

The experiment:

The team used the information and advanced computational methods to construct a tree that traced the most likely evolutionary path of molecular functions through time. At the base of the tree, close to its roots, were the most ancient functions. The most recent were close to the crown.

The observation:

At the base of the tree, corresponding to the origin of life on Earth, were functions related to metabolism and binding. "It is logical that these two functions started very early because molecules first needed to generate energy through metabolism and had to interact with other molecules through binding," Caetano-Anollés explains.

The next major advancements were functions that made the rise of macromolecules possible, which is when RNA might have entered the picture. Next came the machinery that integrated molecules into cells, followed by the rise of functions allowing communication between cells and their environments. "Finally, as you move toward the crown of the tree, you start seeing functions related to highly sophisticated processes involving things like muscle, skin, or the nervous system," Caetano-Anolles says.

Of course if you search for and stack your molecular functions from simplest to most complex, is it a reflection of the order of chronological precedence, or a sorting based on expectation that the most ancient functions and most recent go according to the rules that were written in the computer program?

. . . A handful of simple steps transformed the aldehyde into two compounds resembling adenine- and guanine-containing nucleotides, they report today in Nature Communications. The resemblance wasn’t perfect: In the base of each, a carbon atom was bound to an oxygen atom instead of a hydrogen atom as in the familiar purines.

“It’s nice chemistry,” says Nicholas Hud, an RNA chemist at Georgia Institute of Technology in Atlanta. However, he says, that wayward oxygen atom is a key stumbling block. There’s no simple way to exchange it for hydrogen. And the unconventional purines might have been unable to form RNA analogs with the properties needed to spark life. Powner says he and his colleagues are now looking for solutions. If they succeed, the path from simple chemicals to life will be a whole lot clearer.

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A paradigm-shifting hypothesis could reshape our idea about the origin of life

Date: July 18, 2017

Source: University of California - Santa Cruz

Summary: A new discovery pushes back the time for the emergence of microbial life on land by 580 million years and also bolsters a paradigm-shifting hypothesis that life began, not in the sea, but on land.

While there is still debate about whether life began on land or in the sea, the discovery of ancient microbial fossils in a place like the Pilbara shows that these geothermal areas -- full of energy and rich in the minerals necessary for life -- harbored living microorganisms far earlier than believed.

How proteins evolved billions of years ago, when Earth was devoid of life, has stumped many a scientist. A little do-si-do between amino acids and their chemical lookalikes may have done the trick. Evolutionary chemists tried it and got results by the boatload.

More developments referencing the RNA, this time with depsipeptides.

The new study joins similar work about the formation of RNA precursors on prebiotic Earth, and about possible scenarios for the formation of the first genes.

. . .

To identify the more than 650 depsipeptides that formed, the researchers used mass spectrometry combined with ion mobility, which could be described as a wind tunnel for molecules. Along with mass, the additional mobility measurement gave the researchers data on the shape of the depsipeptides.

Algorithms created by Georgia Tech researcher Anton Petrov processed the data to finally identify the molecules.

To illustrate how potentially bountiful depsipeptides could have been on prebiotic Earth: The researchers had to limit the number of amino acids and hydroxy acids to three each. Had they taken 10 each instead, the number of theoretical depsipeptides could have climbed over 10,000,000,000,000.

In a rock formation called the Saglek Block, Yuji Sano and Tsuyoshi Komiya from the University of Tokyo found crystals of the mineral graphite that contain a distinctive blend of carbon isotopes. That blend suggests that microbes were already around, living, surviving, and using carbon dioxide from the air to build their cells. If the two researchers are right—and claims about such ancient events are always controversial—then this Canadian graphite represents one of the earliest traces of life on Earth.

The Earth was formed around 4.54 billion years ago. If you condense that huge swath of prehistory into a single calendar year, then the 3.95-billion-year-old graphite that the Tokyo team analyzed was created in the third week of February. By contrast, the earliest fossils ever found are 3.7 billion years old; they were created in the second week of March.

Life on Earth began somewhere between 3.7 and 4.5 billion years ago, after meteorites splashed down and leached essential elements into warm little ponds, say scientists. Their calculations suggest that wet and dry cycles bonded basic molecular building blocks in the ponds' nutrient-rich broth into self-replicating RNA molecules that constituted the first genetic code for life on the planet.

Not quite sure what is meant by calculations here, but between this:

The researchers base their conclusion on exhaustive research and calculations drawing in aspects of astrophysics, geology, chemistry, biology and other disciplines. Though the "warm little ponds" concept has been around since Darwin, the researchers have now proven its plausibility through numerous evidence-based calculations.

"Because there are so many inputs from so many different fields, it's kind of amazing that it all hangs together," Pudritz says. "Each step led very naturally to the next. To have them all lead to a clear picture in the end is saying there's something right about this."

and this:

Pearce and Pudritz plan to put the theory to the test next year, when McMaster opens its Origins of Life laboratory that will re-create the pre-life conditions in a sealed environment.

"We're thrilled that we can put together a theoretical paper that combines all these threads, makes clear predictions and offers clear ideas that we can take to the laboratory," Pudritz says.

the suggestion near the beginning of this ongoing thread that someone be able to piece many of the various inputs together appears to be coming to fruition from what is cited from this article.

Chemists have found a compound that may have been a crucial factor in the origins of life on Earth, explains a new report.

Origins-of-life researchers have hypothesized that a chemical reaction called phosphorylation may have been crucial for the assembly of three key ingredients in early life forms: short strands of nucleotides to store genetic information, short chains of amino acids (peptides) to do the main work of cells, and lipids to form encapsulating structures such as cell walls. ...

TSRI chemists have now identified just such a compound: diamidophosphate (DAP).

"We suggest a phosphorylation chemistry that could have given rise, all in the same place, to oligonucleotides, oligopeptides, and the cell-like structures to enclose them," said study senior author Ramanarayanan Krishnamurthy, associate professor of chemistry at TSRI. "That in turn would have allowed other chemistries that were not possible before, potentially leading to the first simple, cell-based living entities."

Researchers in Germany are now arguing that a meteorite impact could have created the molecules that gave life its big break. Their experiments are the first to show that the mechanical energy released during an impact could have transformed simple chemicals into amino acids.1

‘I was standing in front of the Coliseum. Everybody was taking pictures but I was looking at the floor and saw these very round stones,’ he recounts. He took a few of them back to Germany and found that they could replace metal milling balls in his mechanochemical experiments.2

Summary: Scientists have used experiments to retrace the chemical steps leading to the creation of complex hydrocarbons in space. They showed pathways to forming 2-D carbon-based nanostructures in a mix of heated gases.

Chemical compounds needed for the study were not commercially available, said Felix Fischer, an assistant professor of chemistry at UC Berkeley who also contributed to the study, so his lab prepared the samples. "These chemicals are very tedious to synthesize in the laboratory," he said.

At the ALS, researchers injected the gas mixture into a microreactor that heated the sample to a high temperature to simulate the proximity of a star. The ALS generates beams of light, from infrared to X-ray wavelengths, to support a range of science experiments by visiting and in-house researchers.

The mixture of gases was jetted out of the microreactor through a tiny nozzle at supersonic speeds, arresting the active chemistry within the heated cell. The research team then focused a beam of vacuum ultraviolet light from the synchrotron on the heated gas mixture that knocked away electrons (an effect known as ionization).

They then analyzed the chemistry taking place using a charged-particle detector that measured the varied arrival times of particles that formed after ionization. These arrival times carried the telltale signatures of the parent molecules. These experimental measurements, coupled with Mebel's theoretical calculations, helped researchers to see the intermediate steps of the chemistry at play and to confirm the production of pyrene in the reactions.

Mebel's work showed how pyrene (a four-ringed molecular structure) could develop from a compound known as phenanthrene (a three-ringed structure). These theoretical calculations can be useful for studying a variety of phenomena, "from combustion flames on Earth to outflows of carbon stars and the interstellar medium," Mebel said.

Summary: The question of the origin of life remains one of the oldest unanswered scientific questions. A team has now shown for the first time that phase separation is an extremely efficient way of controlling the selection of chemical building blocks and providing advantages to certain molecules.

Molecules in the garage

The effect can also be seen externally: the initially clear solution becomes milky. The lack of water in the oil droplets is like a protection because anhydrides need water to disintegrate back into carboxylic acids.

[Chemist Job] Boekhoven explains the principle of phase separation with an analogy: "Imagine an old and rusty car: Leave it outside in the rain, and it continues to rust and decomposes because rusting is accelerated by water. Put it in the garage, and it stops rusting because you separate it from the rain."

In a way, a similar process occurs in the primordial soup experiment: Inside the oil droplet (garage) with the long-chain anhydride molecules there is no water, so its molecules survive longer. If the molecules compete with each other for energy, again those that can protect themselves by forming oil droplets are likelier to survive, while their competitors get hydrolyzed.

Summary: How did life arise on Earth? Researchers have found among the first and perhaps only hard evidence that simple protein catalysts -- essential for cells, the building blocks of life, to function -- may have existed when life began.

Researchers have designed a synthetic small protein that wraps around a metal core composed of iron and sulfur. This protein can be repeatedly charged and discharged, allowing it to shuttle electrons within a cell. Such peptides may have existed at the dawn of life, moving electrons in early metabolic cycles.Credit: Vikas Nanda/Rutgers University-New Brunswick

Hard Evidence?

The scientists used computers to model a short, 12-amino acid protein and tested it in the laboratory. This peptide has several impressive and important features. It contains only two types of amino acids (rather than the estimated 20 amino acids that synthesize millions of different proteins needed for specific body functions), it is very short and it could have emerged spontaneously on the early Earth in the right conditions. The metal cluster at the core of this peptide resembles the structure and chemistry of iron-sulfur minerals that were abundant in early Earth oceans. The peptide can also charge and discharge electrons repeatedly without falling apart, according to Nanda, a resident faculty member at the Center for Advanced Technology and Medicine.

"Modern proteins called ferredoxins do this, shuttling electrons around the cell to promote metabolism," said senior author Professor Paul G. Falkowski, who leads Rutgers' Environmental Biophysics and Molecular Ecology Laboratory. "A primordial peptide like the one we studied may have served a similar function in the origins of life."

Summary: All living beings need cells and energy to replicate. Without these fundamental building blocks, living organisms could not exist. Little was known about a key element in the building blocks, phosphates, until now. Researchers have now provide compelling new evidence that this component for life was generated in outer space and delivered to Earth in its first one billion years by meteorites or comets.

In an ultra-high vacuum chamber cooled down to 5 K (-450°F) in the W.M. Keck Research Laboratory in Astrochemistry at UH Manoa, the Hawaii team replicated interstellar icy grains coated with carbon dioxide and water, which are ubiquitous in cold molecular clouds, and phosphine. When exposed to ionizing radiation in the form of high-energy electrons to simulate the cosmic rays in space, multiple phosphorus oxoacids like phosphoric acid and diphosphoric acid were synthesized via non-equilibrium reactions.

"On Earth, phosphine is lethal to living beings," said Turner, lead author. "But in the interstellar medium, an exotic phosphine chemistry can promote rare chemical reaction pathways to initiate the formation of biorelevant molecules such as oxoacids of phosphorus, which eventually might spark the molecular evolution of life as we know it."

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Carell’s story starts with only six molecular building blocks—oxygen, nitrogen, methane, ammonia, water, and hydrogen cyanide, all of which would have been present on early Earth. Other research groups had shown that these molecules could react to form somewhat more complex compounds than the ones Carell used.

To make the pyrimidines, Carell started with compounds called cyanoacetylene and hydroxylamine, which react to form compounds called amino-isoxazoles. These, in turn, react with another simple molecule, urea, to form compounds that then react with a sugar called ribose to make one last set of intermediate compounds.

Finally, in the presence of sulfur-containing compounds called thiols and trace amounts of iron or nickel salts, these intermediates transform into the pyrimidines cytosine and uracil. As a bonus, this last reaction is triggered when the metals in the salts harbor extra positive charges, which is precisely what occurs in the final step in a similar molecular cascade that produces the purines, adenine and guanine. Even better, the step that leads to all four nucleotides works in one pot, Carell says, offering for the first time a plausible explanation of how all of RNA’s building blocks could have arisen side by side.

Our prehistoric Earth, bombarded with asteroids and lightening, rife with bubbling geothermal pools, may not seem hospitable today. But somewhere in the chemical chaos of our early planet, life did form. How? For decades, scientists have created miniature replicas of infant Earth in the lab in order to hunt for life's essential ingredients. Now, one of those replicas points to a possible new ingredient in the world's first RNA.

First, some new versions discovered to test.

Recently, however, researchers discovered a way to make versions of adenosine and inosine -- 8-oxo-adenosine and 8-oxo-inosine -- from materials available on primeval Earth. So, Kim and his colleagues set out to investigate whether RNA constructed with these analogs could replicate efficiently.

And while these substitutes failed to perform, the crux per this excerpt is:

nosine enabled RNA [replicated] with high speed and few errors. It "turns out to exhibit reasonable rates and fidelities in RNA copying reactions," the team concluded. "We propose that inosine could have served as a surrogate for guanosine in the early emergence of life."

In biology, folded proteins are responsible for most advanced functions. These complex proteins are the result of evolution or design by scientists. Now scientists have discovered a new class of complex folding molecules that emerge spontaneously from simple building blocks.

Hightlight from within:

Origin-of-life

Proteins have two major folding structures: alpha helices and the beta pleated sheet. 'In protein design, scientists use variations on these themes, like adding an extra helix', says Otto. 'They tend to stick close to what nature has offered.' The new folding structure results in five stacks of five aromatic rings. The entire molecule has a five-fold symmetry. 'However, the other thiol-based structures that we are still studying show yet other types of folding.'

A striking conclusion drawn from the discovery of this new folding molecule is that complexity can emerge spontaneously. 'This is interesting for origin-of-life research: apparently, you can get these complex molecules before biological evolution has started.' The formation of the new molecule is actually driven by folding, explains Otto. 'That is quite special. The energy level of this molecule is very low. This drives the equilibrium from a "random" mixture of small rings towards this specific very stable 15-mer.'